RT Journal Article
SR Electronic
T1 Effects of the Novel Multiple-Action Agent Carvedilol on Severe Nephrosclerosis in Renal Ablated Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 336
OP 344
VO 283
IS 1
A1 Jose C. Rodriguez-Perez
A1 Antonio Losada
A1 Aranzazu Anabitarte
A1 Juan Cabrera
A1 Javier Llobet
A1 Leocadia Palop
A1 Celia Plaza
YR 1997
UL http://jpet.aspetjournals.org/content/283/1/336.abstract
AB Antihypertensive drugs have differing effects on renal hemodynamics and morphology. We analyzed whether the use of a new betaadrenoceptor antagonist and vasodilator, carvedilol (CVD), slows the progression of nephrosclerosis and whether the renoprotective effect as well as reduction in cardiac hypertrophy is dependent on the degree of blood pressure reduction. Fifty-four adult male Sprague-Dawley rats were distributed among five groups: group I served as untreated controls with 5/6 nephrectomy (Nx); group II, sham (no renal ablation or drug treatment); group III, CVD 5 (5/6 Nx and treatment with oral CVD at 5 mg/kg/day); group IV, CVD 10 (5/6 Nx and treatment with oral CVD at 10 mg/kg/day); and group V, CVD 20 (5/6 Nx and treatment with oral CVD at 20 mg/kg/day). Tail-cuff blood pressure and 24-hr urine samples were obtained before and at 3, 5 and 11 weeks of treatment with CVD. At the end of the study period, blood was taken to measure serum creatinine, plasma renin activity and CVD levels, as well as the remnant kidney and heart for morphological studies. There was a significant reduction in 24-hr UProtV in all the CVD-treated groups, and it was increasingly evident with the highest dose used. However, only rats receiving doses of 10 and 20 mg/kg/day of CVD exhibited significant decreases in blood pressure. Elevated serum creatinine levels seen in untreated controls were significantly decreased by CVD in treated rats (P < .01), indicating that glomerular filtration rate was improved by this drug. This was associated with a significant increase in UNaV. Concomitant and significant (P < .01) decreases in plasma renin activity were observed in sham and CVD-treated rats. CVD-treated animals had considerably reduced renal damage (P < .01) and cardiac hypertrophy (P < .01) compared with untreated controls. These data indicate that CVD is effective in delaying progression of renal damage and provides beneficial effects in the remnant kidney and cardiac hypertrophy, even at nonhypotensive doses. The American Society for Pharmacology and Experimental Therapeutics